Secondary Metabolites With Antitumor Activity From Two Mangrove Fungal Endophytes

Mangrove forests constitute a dynamic transition zone between terrestrial and marine habitats and Mangrove plants have to adapt to extreme environmental conditions,including extensive salinity,high temperature and moisture,anaerobic soil,tidal activities and high microbial and faunal competition.Accordingly,mangrove plants host a great variety of endophytes comprising a consortium of soil,marine and freshwater fungi.It has been reported that mangrove endophytic fungi represent the second largest ecological group of marine-derived fungi,with hitherto more than 200 species that have been isolated and identified.Hence,endophytes from mangrove plants have recently attracted considerable attention from natural products chemists looking for new inspirations from nature.The fungal genus of Phomopsis,an important member of mangrove endophytic fungi,contains a number of important bioactive metabolites.The antitumor activities of four Phomopsis strains(xy19,xy20,xy21,xy22)from Thai mangrove were tested by our group.All of them showed potent selective inhibitory activity against HCT-116 and BGC823 cancer cell lines.Accordingly,chemical investigation of the mangrove fungal endophytes,Phomopsis spp.xy21 and xy22 was carried out.As a result,32 compounds were isolated and identified by NMR,HRESIMS and single-crystal X-ray diffraction.Their strctures were elucidated as phomoxanthone I(1),phomoxanthone H(2),dicerandrol A(3),dicerandrol B(4),dicerandrol C(5),phomoxanthone A(6),12-deacetylphomoxanthone A(7),deace-tylphomoxanthone B(8),(3R,5R,5aR,11 aS,12R)-5,5a,7,12-tetrahydroxy-3-methyl-3,4,5,5a-tetrahydro-3,11a-methanooxepi no[3,4-b]chromen-6(1H)-one(9),(1S,2S,3R)-2,8-dihydroxy-1-(hydroxymethyl)-3-methyl-3,4-dihydro-1H-xanthen-9(2H)-one(10),leptosphaerin E(11),methyl-2-(2,6-dihydroxybenzoyl)-3-hydroxy-5-methylbenzoate(12);altechromone A(13),mellein(14),4-hydroxybenzaldehyde(15),(2R,7S,8aS,9R,12 R,12aS)-7-hydroxy-2-methylhexahydro-1H-9,12-epoxybenzo[d]oxecine-4,8,11(2H,5H,8aH)-trione(16),(6aR,9S,9aS)-9-((2S)-1-hydroxy-2-methylbutyl)-3,6a-dimethyl-9,9a-dihydro-6H-furo[2,3-h]isochromene-6,8(6aH)-dione(17),phomopsichalasin D(18),phomopsichalasin E(19),phomopsichalasin F(20),phomopsichalasin G(21)4’-hydroxy-deacetyl-18-deoxycytochalasin H(22),21-O-deacetyl-L-696,474(23),L-696,474(24),deacetylcytochalasin H(25),cytochalasin H(26),epoxycytochalasin H(27),ergosta-7,22-diene-3,5,6-triol(28),ergosta-7,22-diene-3,5-diol,6-methoxy(29),3,5-dihydroxy-ergosta-7,22-dien-6-one(30),ergosta-7,22-dien-6-one,3,5,9-trihydroxy(31),isocyathisterol(32).Among them,compounds 1-2,9-10,16-21 are new ones.All of the isolates were evaluated for the cytotoxicity against eight human cancer cell lines using the MTT method.Compounds 2,6,17 and 20-27 showed potent selectivity antitumor activity.